Several studies have indicated a role of DA in reinforcing effects of drugs and natural reinforcers such as food. A link between DA D2 receptors and obesity through a modification of brain reinforcement mechanisms has also been suggested. One hypothesis suggests that decreased expression of DA D2 receptors decreases the effectiveness of all reinforcers, which is met by a compensatory over ingestion of food. Difficulties in testing the hypothesis arise from the inherent incongruity between the hypothesis that states that reinforcing effects are decreased and the observation that food intake increases. Additionally, a singular test of reinforcing efficacy is not available. Using behavioral economic measures we assessed the reinforcing effects of food under fixed-ratio schedules in DA D2 receptor mutant mice. Behavioral economic theory shows that consumption of a commodity, or demand, is a function of price. Thus, rate of reinforcement (consumption of the commodity) was assessed as a function of the number of required responses (fixed-ratio value, or price of the commodity). The data were fitted with the equation: logQ=logQ0+k(e-Q0C-1), where C = the price of each reinforcer, k = the range of the data, is a free parameter representing the inverse of reinforcer efficacy, and Q0 is a free parameter representing consumption under no-price conditions. The demand curve decreased more steeply in KO than HET or WT mice, indicating lower reinforcing efficacy with DA D2 receptor deletion. Additionally, and consistent with economic theory, these effects were obtained regardless of the type of response (lever press or nose poking response, with effort greater for lever presses). The genetic differences in demand function were reflected in values that were inversely related to DA D2 receptor population (i.e., KO>HET>WT). The data indicate that DA D2 receptors are involved in reinforcement, though the fact that the behavior was initially developed and maintained in KO mice indicates that D2 receptors are not necessary for reinforcement. Clearly the D2 receptor role in reinforcing effects is subtle and requires tools with power for its evaluation. Giving the subjects a meal before sessions (partial satiation) decreased rates of responding, with no significant difference across the three genotypes. Thus the motivational effects of food deprivation, in contrast to the reinforcing effects of food itself, appear largely independent of DA D2 receptor populations. Effects of eliminating reinforcers (extinction) were also independent of genotype. Because all stimuli other than those arising from food delivery were retained during extinction, the primary stimulus contributing to the pause was the food, and likely those arising from its consumption. These findings support the view that reinforcing stimuli serve multiple stimulus functions, and suggest further studies of extinction in which food is delivered independently of responding. Finally, the DA D2 receptor antagonist, (-)eticlopride dose-dependently decreased responding in all genotypes, with (-)eticlopride more potent than its (+)enantiomer in all but KO mice, where the enantiomers were equipotent. This pharmacology substantiates that effects of (-)eticlopride were specifically due to DA D2 receptor antagonism, and not due to an off-target action. The opposing effects of DA D2 receptor blockade and extinction indicate that the effects of the drug are not specifically due to antagonism of the reinforcing effects of food presentation. The role of DA D3 receptors in the subjective effects of cocaine was examined by training mice to discriminate cocaine from saline injections under a fixed-ratio 10 schedule of food reinforcement. The cocaine dose-effect curves were not different in mice with and without DA D3 receptors. The putative D3 partial agonist, BP897, and antagonists (NGB2904, nafadotride) were tested alone and with cocaine. None of the drugs produced cocaine-like responding in either line of mice. BP897 significantly shifted the cocaine curve 3.5 and 1.5-fold to the right in WT and KO mice, respectively. The greater shift in the cocaine dose-effect curve in WT mice suggests a relatively small role for DA D3 receptors in the subjective effects of cocaine. Together with the similarity of the cocaine effects in the two lines of mice, these results indicate a minimal role of DA D3 receptors in the subjective effects of cocaine. The putative DA D3 antagonist, NGB2904 significantly but modestly (2-fold) potentiated the subjective effects of cocaine in WT mice, but had no significant effect on cocaine in KO mice. Nafadotride, and the DA D2 receptor selective antagonist, L741626, each shifted the cocaine curve to the right comparably in both lines of mice. These data suggest some DA D3 agonist actions of NGB2904. In addition, although nafadotride is often claimed to be a DA D3 antagonist, the present results are consistent with its DA D2 antagonist effects, and suggest that it is a non-selective antagonist. The antagonist effects of L741626 indicate a prominent role of DA D2 receptors in the subjective effects of cocaine. The lack of profound effects of the DA D3 receptor in modulating the effects of cocaine has lead to studies looking for a role of DA D3 receptors in other behaviors. D2-like agonists (drugs acting at any of DA D2, D3 and D4 receptors) have been shown to induce yawning in rodents and primates, and penile erections (PE) in rodents. This latter effect has been suggested to be specifically mediated by DA D4 receptors, whereas yawning is thought to be mediated by DA D3 receptors. The roles of these receptors in the effects of DA D2-like agonists were assessed pharmacologically and genetically. All of the agonists having effects at DA D3 receptor induced dose-dependent increases in PE and yawning, while significant increases in PE or yawning were not observed with selective D4 agonists. Likewise, D2, D3, and D4 antagonists were assessed for their capacity to alter apomorphine-induced PE and yawning. The selective D3 antagonist, PG01037, inhibited the induction of PE and yawning, whereas the D4 antagonist, L745870, did not alter apomorphine effects. A role for the D3 receptor in PE was further supported as apomorphine was equipotent at inducing PE in D4 receptor WT and KO mice, and those effects were blocked by the D3 antagonist, PG01037. Together, these studies indicate that D2-like agonist-induced PE and yawning are induced by D3 DA receptors, and fail to support a role for the D4 receptor in either effect. To confirm a role for DA D3 receptors in yawning we examined the effects of several DA agonists in WT and DA D3 receptor KO mice. In contrast to effects obtained with rats, none of the agonists produced yawning in mice. Though yawning was not produced in the mice by the dopaminergic agonists, it was reliably elicited by administration of the cholinergic agonist, physostigmine, in both rats and mice indicating that the lack of effect of the DA agonists was not due to the absence of the response in mice. The DA agonists similarly were ineffective in producing yawning in DA D2 receptor KO mice or their WT controls, indicating that the absence of yawning in mice was not due to an inhibitory effect of DA D2 receptors. The DA agonists tested decreased locomotor activity at low to intermediate doses in WT but not D2 receptor KO mice. The decreases in locomotor activity were profound in that they were obtained across a 1,000- to 10,000-fold range of doses, with the decreases normally followed by increases in activity at higher doses. Further, decreases in locomotor activity were comparable in D3 receptor KO and WT mice. These data suggest that the decreases in locomotor activity were due to actions at DA D2 receptors.